Total Synthesis of Fontanesine B and Its Isomer: Their Antiproliferative Activity against Human Colorectal Cancer Cells

Abstract

A concise synthesis of pyrano[3,2‐e]indole alkaloid fontanesine B by a Fischer indolization is described. This key Fischer indolization starts with the pyran‐ring and alkene intact, facilitating potential synthetic applications. Furthermore, fontanesine B and its isomer were evaluated for in vitro antiproliferative activity against human colorectal cancer cells. The isomer of fontanesine B showed higher antiproliferative activity than the natural product, fontanesine B (2).

A Comprehensive Review on Pyranoindole-containing Agents

“…They were isolated from the stem bark and leaf fractions of Conchocarpus fontanesianus, collected in Brazil by Queiroz and co-workers [24]. The antiproliferative effect of fontanesine B was evaluated on human colorectal cancer cells, DLD-1, by water-soluble tetrazolium salt (WST-1) assay and no inhibitory effects were recorded [25]. The total synthesis of fontanesine B has been recently reported [26].…”

“…Abe et al (2019) [25] reported the antiproliferative activity studies of natural fontanesine B (6b, Fig. 11) and its synthetic cyclic isomer 3a (Fig.…”

“…Compound 3a (hydropyrano[2,3-f]indole, series 3) was studied as an isomer of fontanesine B (pyrano[3,2e]indole, series 6). The synthesis was reported by Abe et al [25] (Scheme 2). When 9 was refluxed in AcOH, a mixture of 6b and 3a was obtained in 71% yield (6b/3a = 25:75).…”

Synthesis of indole derivatives as prevalent moieties present in selected alkaloids

“…A previous investigation on the leaf extracts of C. fontanesianus stated their cytotoxic, anti-fungal, and also anti-microbial activities, but the potent principles were not developed. 220 In 2019, Abe et al reported 221 a short synthesis of pyrano[3,2- e ]indole alkaloid fontanesine B via a Fischer indolization. The isomer of fontanesine B exhibited a greater anti-proliferative property in comparison with the natural product, fontanesine B (187).…”

“…Among the various acids, propionic acid was the most effective acid at providing the desired cyclized products (88% yield, 187/188 = 33 : 67) ( Scheme 24 ). 221 …”